Microfluidic-based speckle analysis for sensitive measurement of erythrocyte aggregation: A comparison of four methods for detection of elevated erythrocyte aggregation in diabetic rat blood
Abstract:Biochemical alterations in the plasma and red blood cell (RBC) membrane of diabetic blood lead to excessive erythrocyte aggregation (EA). EA would significantly impede the blood flow and increase the vascular flow resistance contributing to peripheral vascular diseases. In this study, a simple microfluidic-based method is proposed to achieve sensitive detection of hyperaggregation. When a blood sample is delivered into the device, images of blood flows are obtained with a short exposure time for a relatively l… Show more
“…By applying shear stress to the blood sample with external driving systems (i.e., an SP [34], pinch valve [16], or stirring motor [35]), the RBCs in the blood sample are aggregated or disaggregated, depending on the shear rate. Several quantification methods, such as light intensity (i.e., transmission, and back-scattering) [16], electrical conductivity [36,37], microscopic RBC images [38][39][40], ultrasonic images [41], and optical tweezers [42] have been suggested for obtaining temporal variations of RBCs aggregation. As another approach, RBC aggregation can be quantified by measuring the sedimentation distances of RBCs in a blood sample during a specific duration (i.e., ESR).…”
To quantify the variation of red blood cells (RBCs) or plasma proteins in blood samples effectively, it is necessary to measure blood viscosity and erythrocyte sedimentation rate (ESR) simultaneously. Conventional microfluidic measurement methods require two syringe pumps to control flow rates of both fluids. In this study, instead of two syringe pumps, two air-compressed syringes (ACSs) are newly adopted for delivering blood samples and reference fluid into a T-shaped microfluidic channel. Under fluid delivery with two ACS, the flow rate of each fluid is not specified over time. To obtain velocity fields of reference fluid consistently, RBCs suspended in 40% glycerin solution (hematocrit = 7%) as the reference fluid is newly selected for avoiding RBCs sedimentation in ACS. A calibration curve is obtained by evaluating the relationship between averaged velocity obtained with micro-particle image velocimetry (μPIV) and flow rate of a syringe pump with respect to blood samples and reference fluid. By installing the ACSs horizontally, ESR is obtained by monitoring the image intensity of the blood sample. The averaged velocities of the blood sample and reference fluid (<UB>, <UR>) and the interfacial location in both fluids (αB) are obtained with μPIV and digital image processing, respectively. Blood viscosity is then measured by using a parallel co-flowing method with a correction factor. The ESR is quantified as two indices (tESR, IESR) from image intensity of blood sample (<IB>) over time. As a demonstration, the proposed method is employed to quantify contributions of hematocrit (Hct = 30%, 40%, and 50%), base solution (1× phosphate-buffered saline [PBS], plasma, and dextran solution), and hardened RBCs to blood viscosity and ESR, respectively. Experimental Results of the present method were comparable with those of the previous method. In conclusion, the proposed method has the ability to measure blood viscosity and ESR consistently, under fluid delivery of two ACSs.
“…By applying shear stress to the blood sample with external driving systems (i.e., an SP [34], pinch valve [16], or stirring motor [35]), the RBCs in the blood sample are aggregated or disaggregated, depending on the shear rate. Several quantification methods, such as light intensity (i.e., transmission, and back-scattering) [16], electrical conductivity [36,37], microscopic RBC images [38][39][40], ultrasonic images [41], and optical tweezers [42] have been suggested for obtaining temporal variations of RBCs aggregation. As another approach, RBC aggregation can be quantified by measuring the sedimentation distances of RBCs in a blood sample during a specific duration (i.e., ESR).…”
To quantify the variation of red blood cells (RBCs) or plasma proteins in blood samples effectively, it is necessary to measure blood viscosity and erythrocyte sedimentation rate (ESR) simultaneously. Conventional microfluidic measurement methods require two syringe pumps to control flow rates of both fluids. In this study, instead of two syringe pumps, two air-compressed syringes (ACSs) are newly adopted for delivering blood samples and reference fluid into a T-shaped microfluidic channel. Under fluid delivery with two ACS, the flow rate of each fluid is not specified over time. To obtain velocity fields of reference fluid consistently, RBCs suspended in 40% glycerin solution (hematocrit = 7%) as the reference fluid is newly selected for avoiding RBCs sedimentation in ACS. A calibration curve is obtained by evaluating the relationship between averaged velocity obtained with micro-particle image velocimetry (μPIV) and flow rate of a syringe pump with respect to blood samples and reference fluid. By installing the ACSs horizontally, ESR is obtained by monitoring the image intensity of the blood sample. The averaged velocities of the blood sample and reference fluid (<UB>, <UR>) and the interfacial location in both fluids (αB) are obtained with μPIV and digital image processing, respectively. Blood viscosity is then measured by using a parallel co-flowing method with a correction factor. The ESR is quantified as two indices (tESR, IESR) from image intensity of blood sample (<IB>) over time. As a demonstration, the proposed method is employed to quantify contributions of hematocrit (Hct = 30%, 40%, and 50%), base solution (1× phosphate-buffered saline [PBS], plasma, and dextran solution), and hardened RBCs to blood viscosity and ESR, respectively. Experimental Results of the present method were comparable with those of the previous method. In conclusion, the proposed method has the ability to measure blood viscosity and ESR consistently, under fluid delivery of two ACSs.
“…Figure 3a shows the temporal variation in flow rate evaluated based on velocity fields measured by a micro-particle image velocimetry (PIV). Details of the flow rate measurement are described in detail in our previous study 20 .Figure 3Variation in RBC aggregation measured by analyzing image intensity. ( a ) Temporal variation in flow rate of blood samples estimated by micro-PIV technique.…”
Section: Resultsmentioning
confidence: 99%
“…An ESR value reflects certain hemorheological conditions, such as RBC aggregation, RBC deformability, and hematocrit 20 . However, measurement of ESR values is a tedious process.…”
Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.
“…RBC aggregate size distributions have also been considered in the studies of Mehri et al [1] and Yeom et al [2] . Yeom et al, used a technique based on counting the number of RBCs per aggregate at low haematocrits (10%), in a very thin chamber (10 µm height) while Mehri et al quantified the distribution of RBC aggregates in a rectangular geometry (110x60µm width and height) and at low haematocrits (5, 10 and 15%) using image processing techniques.…”
Section: Introductionmentioning
confidence: 99%
“…Studying blood flow at such scales allows key flow and structural characteristics of blood, arising from its multiphase nature, to be studied in great depth [1,2]. The complex characteristics of microscale blood flow are mainly due to the presence of red blood cells (RBCs) which constitute the majority of the cellular matter of blood.…”
Red blood cell aggregation plays a key role in microcirculatory flows, however, little is known about the transport characteristics of red blood cell aggregates in branching geometries. This work reports on the fluxes of red blood cell aggregates of various sizes in a T-shaped microchannel, aiming to clarify the effects of different flow conditions in the outlet branches of the channel. Image analysis techniques, were utilised, and moderately aggregating human red blood cell suspensions were tested in symmetric (~50-50%) and asymmetric flow splits through the two outlet (daughter) branches. The results revealed that the flux decreases with aggregate size in the inlet (parent) and daughter branches, mainly due to the fact that the number of larger structures is significantly smaller than that of smaller structures. However, when the flux in the daughter branches is examined relative to the aggregate size flux in the parent branch an increase with aggregate size is observed for a range of asymmetric flow splits. This increase is attributed to size distribution and local concentration changes in the daughter branches. The results show that the flow of larger aggregates is not suppressed downstream of a bifurcation, and that blood flow is maintained, for physiological levels of red blood cell aggregation.
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